1. Field of the Invention
The present invention is directed to compositions and methods for treating diseases and disorders of patients and, in particular, compositions, uses of the composition and methods for treating infections of patients with lysostaphin and synergistic combinations of lysostaphin and conventional treatments such as antibiotics, antibodies or other enzymes. The invention is also directed to methods for the treatment of infections, and in particular non-Staphylococcal infections, with lysostaphin and/or altered forms of lysostaphin that possess increased efficacy against infections as compared to wild-type lysostaphin. The altered forms preferably generate a minimal or no immune response in a patient as compared with wild-type lysostaphin.
2. Description of the Background
Staphylococcus aureus (SA) is a major cause of severe infections of animals and people. In humans, a skin infection may rapidly progress from a mild local infection or wound to sepsis, multi-organ system failure, shock and death within hours. Surgical patients, diabetics and premature infants are also highly susceptible to infection and individuals with catheters, artificial valves and other foreign bodies may develop colonization of these devices that are very difficult treat. Over the last several years, SA has become resistant to many key antibiotics including the first line penicillins (e.g. multi-drug resistant Staphylococcus aureus or generally MRSA). These organisms have spread around the world and MRSA is a major cause of both community and hospital acquired infections.
Lysostaphin is an effective agent for treating SA infections in that it attacks both actively growing and quiescent Staphylococcal bacterial cells. This enzyme cleaves the pentaglycine bridge in the cell wall of SA. The cell walls of other microbes such as M. tuberculosis (MTB) are very different from SA and many antibiotics that are effective for treating SA infections do not work well for treating MTB. The cell wall of MTB is about 60% lipid and can evade the immune system and render many common antibiotics ineffective. MTB is also difficult to treat because it replicates only about every 20 hours and can even become dormant and replicate little if at all. These characteristics and the rapid rise of strains that are resistant to current anti-MTB antibiotics make effective therapy increasingly difficult.
There is a need for new approaches for treating MTB and other microbial infections.